Oral infections may remain localized or spread through connective tissues to other sites. Very little is known about the bacterial or host factors that contribute to the connective tissue invasion by extra-cellular microorganisms. These studies are designed to define the host/parasite interactions with Bacteroides. The studies in this Subproject will also provide information on evasion of nonspecific host defenses. These may be crucial in designing future therapeutic approaches that are based on modulation of nonspecific non-cellular host defense mechanisms. The approaches would be of particular importance to the increasing number of hosts with deficiencies in leukocytes and/or in the immune system. We have identified strains of Bacteroides gingivalis that when injected subcutaneously in mice produce either a localized lesion or spread through connective tissues. This invasion occurs rapidly in the non-immunized animal and bacteria are seen spreading in connective tissue in the absence of polymorphonuclear cell infiltrate. Thus, it appears that the invasive strains gain advantage because they have the ability to evade nonspecific non- cellular host defense mechanisms. Our approach will investigate the host defense mechanisms evaded by utilizing comparisons between invasive and noninvasive B. gingivalis strains as well as other Bacteroides strains yet to be identified that possess invasive potential. One of the specific aims of this project is to characterize further the mouse abscess model so that invasion can be assessed quantitatively on a histologic basis. Then it will be determine whether there are differences between noninvasive and invasive organisms evading the following host defense: a) iron restriction; b) serum bactericidal activity and c) connective tissue integrity. As the last specific aim we will attempt to define the bacterial antigens or products that are involved in invasion and/or evasion of nonspecific host defense mechanisms. These studies will be integrated with the investigators in Project II (Bacterial Virulence Factors).